Antibiotics-Basel
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2025
·Vol. 14
·期 5
·499
·
IF 4.6
Liyang Wang,Junying He,Hanzhong Feng,Qian Li,Meirong Song,Haoran Gou,Yongxing He,Kui Zhu
Background:Fungal infections pose an increasingly predominant threat to human and animal health. Modified compounds derived from chemo-diverse natural products offer enhanced therapeutic efficacies and promising approaches to combat life-threatening fungal pathogens.Methods:We performed biosynthetic gene clusters analysis of 2,4-diacetylchloroglucoside (DAPG) in 4292 shotgun metagenomes samples from the healthy and diseased skin. Then, we assessed the antifungal activity of DAPG and the derivative 2,4-diproylphloroglucinol (DPPG) against pathogenic fungi by minimum inhibitory concentrations. The inhibitory effects of DPPG were measured using hyphal growth assay and spore germination assay. Concurrently, the mechanism of DPPG onAspergillus fumigatuswas investigated in membrane permeability and fluidity. The therapeutic efficacy was evaluated in aGalleria mellonellainfection model.Results:We observed a significantly higher abundance of bacteria harboring DAPG biosynthetic clusters on healthy skin compared to diseased skin. Further, we designed and synthesized a series of phloroglucinol derivatives based on DAPG and obtained an antifungal candidate DPPG. DPPG not only exhibited robust antifungal activity againstAspergillusspp. andCandidaspp. but also impaired hyphal growth and spore germination ofA. fumigatusin vitro. A mechanism study showed that DPPG reduced membrane fluidity and increased the leakage of cellular contents, resulting in membrane perturbation and fungal death. Lastly, the therapeutic efficacy of DPPG was confirmed in aG. mellonellainfection model.Conclusions:Our study demonstrates that DPPG is a potent scaffold to combat invasive fungal infections.
研究领域:
微生物学
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药理学
·
感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2017
·Vol. 9
·期 35
·5101-5107
·
IF 1.9
Rongwei Yan,Leilei Zhao,Yanfei Li,Yong Zou,Xinjun Xu
As a novel injection preparation, propofol liposomes have extensive application prospects in clinical practice, and lipid components in them need to be quantified for quality control. In this study, a simple and accurate GC-FID method coupled with a methyl esterification pretreatment was developed for simultaneous determination of three main excipients (tricaprylin, TA; dipalmitoyl phosphatidylglycerol, DPPG; 2-dierucoyl-sn-glycero-3-phosphocholine, DEPC) in propofol liposomes with stearic acid used as the internal standard (IS). Response surface methodology was utilized for optimizing three factors of the methyl esterification reaction (the temperature, BF3 concentration and reaction time were optimized to be 75.0 °C, 14.5% and 6.5 min, respectively). Under optimum conditions, the average methyl esterification rate of the three analytes reached 96.43 ± 0.16% (n = 3). Moreover, multiple sample solutions could be simultaneously prepared, which would promote the efficiency and accuracy of quantitative analysis. Three calibration curves had good linear regression (r > 0.9999) within the tested ranges, the average recoveries ranged from 98.64% to 102.44% and the RSDs of the precision, repeatability, stability and recoveries were all below 1.53%. Finally, the validated method was successfully applied to the quantitative analysis of the three analytes in six batches of propofol liposomes.
研究领域:
药学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Jiajie Hu,Xinrui Li,Meng Li,Yazhuo Shang,Yifan He,Honglai Liu
Air pollution has become increasingly serious. Fine particulate matter (PM2.5) is the most well-known air pollutant, which leads to some common respiratory diseases when inhaled into the lungs to certain concentration. However, there is a lack of research on the process of dynamically monitoring the real-time effect of nanoparticles on the pulmonary surfactant monolayer. In this study, the DPPC/DPPG monolayer is prepared by the Langmuir method to simulate the lung surfactant monolayer during respiration and the carbon nanoparticles are introduced to the monolayer under different surface pressures to simulate the real dynamic process of inhaling nanoparticles during breathing. The effect of carbon nanoparticles on the surface behavior of DPPC/DPPG monolayer in real-time was examined in details by a combination of surface pressure (π)-area (A) isotherms, compressibility modulus ( C s - 1 )-surface pressure (π) isotherms and the Brewster angle microscopy (BAM). The results have shown that the introduction of carbon nanoparticles under different surface pressures affects the properties of lipid monolayers. The added carbon nanoparticles under lower surface pressure are easy to penetrate the lipid molecules to inhibit monolayer phase transition. When the carbon nanoparticles are introduced to the monolayer under higher surface pressure, they tend to self-aggregate to reduce the monolayer stability rather than interact with lipid tail chains. This work not only confirms the exotic hydrophobic carbon nanoparticles retain in the DPPC/DPPG monolayer irreversibly and affect the surface behavior of monolayer during respiration, but also opens a new idea for real-time monitoring of the effects of PM2.5 on lung health.
研究领域:
生物物理学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2016
·
IF 2.857
Chun Liu,Fenfen Cheng,Yingen Sun,Hongyu Ma,Xiaoquan Yang
An alkaline isoform of the PR-5 protein (designated GmOLPc) has been purified from soybean hulls and identified by MALDI-TOF/TOF-MS. GmOLPc effectively inhibited in vitro the growth of Phytophthora soja spore and Pseudomonas syringae pv glycinea. The antimicrobial activity of GmOLPc should be mainly ascribed to its high binding affinity with vesicles composed of DPPG, (1,3)-β-d-glucans, and weak endo-(1,3)-β-d-glucanase activity. From the 3D models, predicted by the homology modeling, GmOLPc contains an extended negatively charged cleft. The cleft was proved to be a prerequisite for endo-(1,3)-β-d-glucanase activity. Molecular docking revealed that the positioning of linear (1,3)-β-d-glucans in the cleft of GmOLPc allowed an interaction with Glu83 and Asp101 that were responsible for the hydrolytic cleavage of glucans. Interactions of GmOLPc with model membranes indicated that GmOLPc possesses good surface activity which could contribute to its antimicrobial activity, as proved by the behavior of perturbing the integrity of membranes through surface hydrophobic amino acid residues (Phe89 and Phe94).
研究领域:
植物病理学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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